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Aetiology of congenital heart disease explained


Researchers at Karolinska Institutet have identified the mechanisms behind the serious, congenital heart condition that can sometimes develop in children of women with a rheumatic disease.

This serious form of congenital heart disease, known as AV heart block, develops when a certain type of antibody is transferred from the mother to the foetus during pregnancy. The antibodies are targeted against endogenous proteins and cause the inflammation and calcification of the foetal cardiac conduction system. One in three of such cases are fatal to the foetus, and approximately 70 per cent of the babies born alive require life-long pacemaker treatment.

The mothers normally have a rheumatic disease, such as Sjögren’s syndrome or SLE. In virtually all cases of congenital heart block, the mother produces antibodies against the Ro and La autoantigens, but in only 2-5 per cent of pregnancies amongst Ro and La positive women does this heart condition arise.

This study has identified the specific antibody that causes the damage, and explained its mechanism of action. The antibody targets a specific part of the Ro protein known as p200. The study shows that the level of p200 antibodies in the mother correlates with the degree of damage to the heart. The results have been further confirmed in studies on rats and in cell cultures. Cultivated heart cells, cardiomyocytes, were seriously affected in their calcium balance when exposed to specific p200 antibodies. The cells were rendered unable to accumulate calcium, which ultimately led to cell death, apoptosis.

Knowledge of how this congenital heart condition arises will go a long way towards helping scientists develop better screening, risk assessment and treatment techniques. This is particularly important as early intervention has proved to restrict the extent of the damage, thus preventing pacemaker dependence or foetal death.

“We believe that the antibody we’ve identified can be used as a marker for identifying the mothers who are at a high risk of developing this complication during pregnancy,” says associate professor Marie Wahren-Herlenius. “We’re now working together with Karolinska University Hospital on designing a suitable method for this.”

Tina Zethraeus | alfa
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